title: Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity.
abstract: Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45cm(3) of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL. Electronic address: peterson.jennifer2@mayo.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Peterson
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Buskirk
authors.affiliation: Section of Biostatistics, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heckman
authors.affiliation: Section of Biostatistics, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Nancy N
authors.initials: NN
authors.lastname: Diehl
authors.affiliation: Section of Biostatistics, Mayo Clinic Florida, Jacksonville, FL; Department of Radiation Oncology, Southern Ohio Medical Center, Portsmouth, OH.
authors.forename: Johnny R
authors.initials: JR
authors.lastname: Bernard
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Tzou
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Henry E
authors.initials: HE
authors.lastname: Casale
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Bellefontaine
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Christopher
authors.initials: C
authors.lastname: Serago
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Siyong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Vallow
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Larry C
authors.initials: LC
authors.lastname: Daugherty
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059351:Organ Sparing Treatments / Q000379:methods; D058958:Organs at Risk / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology* / Q000517:prevention & control; D011835:Radiation Protection / Q000379:methods; D011859:Radiography; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods*; D012002:Rectal Diseases / Q000209:etiology* / Q000517:prevention & control; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
keywords: Prostate; Radiotherapy; Toxicity